Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure and cardiovascular mortality in hemodialysis patients

Int J Med Sci. 2014 May 10;11(7):726-31. doi: 10.7150/ijms.8590. eCollection 2014.

Abstract

Objective: Nrf2 is a transcription factor that regulates the expression of antioxidant genes. This study aimed to investigate the association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (-653A/G) and rs6721961 (-617C/A), with laboratory data and mortality in hemodialysis (HD) patients.

Methods: Blood samples were obtained from 216 HD patients (119 males and 97 females; 60 diabetics and 156 non-diabetics) with mean age of 60.3±13.3 (SD) years, and mean HD duration of 9.10±8.28 years. Genotyping was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay.

Results: As for rs35652124, diastolic blood pressure (BP) was significantly high in total AA carriers. β2-microglobulin was significantly low in male AA carriers. Systolic BP, diastolic BP and albumin were significantly high in female AA carriers. As for 6721961, systolic BP and diastolic BP were significantly high in female AA carriers. Cox proportional hazard analysis adjusted for age, HD duration, diabetes and Kt/V demonstrated that rs35652124 AA carriers showed higher cardiovascular mortality than (GG+GA) carriers.

Conclusion: Nrf2 SNPs were associated with BP in Japanese HD patients. More notably, rs35652124 was associated with cardiovascular mortality in these patients.

Keywords: Nrf2; blood pressure; cardiovascular mortality.; hemodialysis; polymorphism.

MeSH terms

  • Aged
  • Blood Pressure / genetics*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / mortality
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics*
  • Polymorphism, Single Nucleotide
  • Renal Dialysis / adverse effects*

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human